Stereoselective Sequence toward Biologically Active Fused Alkylidenecyclobutanes

Abstract

Combining an efficient preparation of cyclobutenylmetal species, high-yielding cross-coupling reactions, and highly diastereoselective [4 + 2]-cycloaddition led to opening a new route toward the synthesis of fused alkylidenecyclobutanes containing up to five consecutive stereocenters. New complex architectures, analogues to protoilludane skeletons, were obtained in a very efficient manner and with a minimum number of steps starting from commercial sources and were tested for their cytotoxicity against leukemia cell lines HL60.

Broadening the Scope of the Gold‐Catalyzed [2+2] Cycloaddition Reaction: Synthesis of Vinylcyclobutenes and Further Transformations

“…As expected,[1f], [3a] 1‐vinylcyclobutenes 3a and 3s underwent Diels–Alder cycloaddition with maleic anhydride ( 8 ) to give penta‐ or tetracyclic compounds 9a and 9b , respectively, which contain a fused tricyclic core related to the protoilludane family of natural products (Scheme ).…”

“…Different functionalities in these small rings broaden their potential synthetic versatility. In particular, 1‐vinylcyclobutenes have been shown to be valuable synthons to create structural complexity . Among the methods to generate 1‐alkenyl‐substituted cyclobutenes, the intermolecular [2+2] cycloaddition reaction of 1,3‐enynes with alkenes is a convenient straightforward strategy.…”

Uncommon Four‐Membered Building Blocks – Cyclobutenes, Azetines and Thietes

“…Complex structures 38 possessing up to five consecutive stereocenters were obtained in great yields and excellent diastereoselectivities that can be explained by an endo‐model of the cycloaddition in which the maleic derivative approaches from the least hindered diastereotopic face of the diene (away from the R 2 group) in order to minimize steric interactions [75] …”

Rapid Assembly of Protoilludane Skeleton through Tandem Catalysis: Total Synthesis of Paesslerin A and Its Structural Revision

“…It is known that the hydroxy substituent at the 6/4 ring juncture would be important for the biological activity from the structure–activity relationship analysis. Because of the characteristic tricyclic structure of protoilludanes, many researchers have investigated the synthetic studies . Most of these are directed to the synthesis protoilludanes having no hydroxy group at the 6/4 ring juncture.…”